N-[4-(2, 6-dimethylpyrimidyl)]3, 5-dinitrobenzamide



United States Patent 3,360,516 N-[4-(2,6-DIMETHYLPYRIMIDYL)]3,5- DINITROBENZAMIDE Guy H. Harris, Concord, Calif., Patricia I. Traylor, Cambridge, Mass., and Bryant C. Fischback, Walnut Creek, Calif., assignors to The Dow Chemical Company, Midland, Micl1., a corporation of Delaware No Drawing. Continuation of application Ser. No. 770,579, Oct. 30, 1958, now Patent No. 3,152,136, dated Oct. 6, 1964. This application June 23, 1961, Ser. No. 119,023

1 Claim. (Cl. 260--256.4)

This application is a continuation of applicants copending application Ser. No. 770,579, filed Oct. 30,1958, now US. Patent 3,152,136.

This invention is concerned with dinitroaroylamide compounds corresponding to the formula In this and succeeding formulae, R represents hydrogen, methyl, ethyl or methoxy, and X represents a nonacid monoheterocyclic organic radical. The expression, nonacid monoheterocyclic aromatic radical, is employed in the present specification and claims to refer to the fully unsaturated monocyclic radicals containing from 5 to 6 3,360,516 Patented Dec. 26, 1967 "ice pletion of the reaction. During the course of the reaction, a solid material usually precipitates in the reaction mixaqueous solution of an alkali metal salt such as sodium carbon atoms in the ring including no morethan three j hetero-atoms from the group consisting of nitrogen, oxygen and sulfur. (These new compounds are crystalline solids which are somewhat soluble in many organic solvents and water. The compounds are useful as parasiticides and are adapted to be employed in dust and liquid compositions for the control of a number of helminth, insect, fungal and protozoan organisms such as 'Eim'eria tenella and Eimeria necatrix.

1 O O (l5 {Chlorine or I Bromine oiN with an amine compound corresponding to the formula X-NH Representative amine compounds include aminopyridine, aminopicoline, aminolutidine, 2-aminothiazole, aminofuran, aminothiophene, aminopyrrole, aminodiazole, 2-aminooxazole, 3-amino-1,2,4-triazole, 2- aminopyrazine, 3-aminopyridazine and 4-aminopyrin1idine. The contacting of the reactants is carried out in an organic reaction medium such as water or diethyl ether. The reaction is somewhat exothermic and takes place smoothly at the temperature range of from 10 to 80 C. with the production of the desired product and hydrogen halide of reaction. This hydrogen halide appears in the reaction mixture as a hydrogen halide salt of the amine reagent. The temperature may be controlled by regulating the rate of contacting the reactants and by external cooling. Good results are obtained when employing one molecular proportion of acid halide with at least one molecular proportion of theamine reagent.

In carrying out the reaction, the reactants are contacted portionwise one with the other in the reaction solvent and the resulting mixture maintained for a short period of time at the contacting temperature range to insure combicarbonate to separate water soluble impurities such as amine hydrohalide and obtain the desired product as a crystalline residue. The produce may be further purified by conventional methods such as washing with water and recrystallization from organic solvents.

The following examples illustrate the invention but are not to be construed as limiting the same.

EXAMPLE 1 N-(2-pyridyl) 3,5-dinitro-0-t0luamz'de OzN 3,5-dinitro-o-toluyl chloride (24.5 grams; 0.1 mole) was added portionwise with stirring to 9.9 grams (0.105

mole) of 2-aminopyridine dissolved in 300 milliliters of I water. The addition was carried out over a period of 15 minutes and at a temperature of from 20 to 30 C. Stirring was thereafter continued for one hour at room temperature to complete the reaction.- During the course of the reaction, a solid material precipitated in the reaction mixture. Upon completion of the reaction, the solid was separated by filtration and successively recrystallized from ethanol and aqueous methanol. The recrystallized material was thereafter suspended for one hour in aqueous 10 percent sodium bicarbonate and thereafter washed with water and the washed product recrystallized from ethanol. As a result of these operations, there was obtained an N-(Z-pyridyl) 3,5-dinitro-o-toluamide product as a crystalline solid melting at 183184 C., and having a carbon content and hydrogen content of 51.3 percent and 3.35 percent, respectively as compared to theoretical contents of 51.7 percent and 3.34 percent.

EXAMPLE 2 N-(Z-thiazolyl) 3,5-dinitr0-0-t0luamide OzN A solution containing 24 grams (0.24 mole) of 2- aminothiazole in 200 milliliters of ether'was added slowly portionwise with stirring to 24.5 grams (0.1 mole) of 3,5-dinitro-o-toluyl chloride dissolved in milliliters of toluene. The addition was carried out over a period of 10 minutes and at a temperature of from 55 to 60 C. During the addition, a solid material precipitated in the reaction mixture. Upon completion of the addition, the solid was separated by filtration, recrystallized from glacial acetic acid, and the recrystallized material successively washed with dilute aqueous sodium bicarbonate and water. As a result of these operations, there was obtained an N-(Z-thiazoyl) 3,5-dinitro-o-toluamide product as a crystalline solid melting at 271.5272.5 C., and having a carbon content of 43.3 percent and a sulfur content of percent and 10.4 percent, respectively.

3 EXAMPLE 3 N Z-gammwpicolyl 3,5 -dinitr-0-t0luamide I O H H l N CN OzN U I CH;

A solution containing 24.5 grams (0.1 mole) of 3,5- dinitro-o-toluyl chloride in 700 milliliters of diethyl ether was added slowly portionwise to 10.8 grams (0.1 mole) of 2-amino-4-picoline dissolved in 500 milliliters of diethyl ether. The addition was carried out over a period of 60 minutes and at a temperature of from 20 to 25 C. During the addition, a solid separated in the reaction mixture. Upon completion of the addition, the solid was separated by filtration, and the separated product washed with aqueous 10 percent sodium bicarbonate and thereafter recrystallized -from ethanol. As a result of these operations, there was obtained an N-(Z-gammapicolyl) 3,5- dinitro-o-toluamide product as a crystalline solid melting' at 207.5-208.5 C. and having a carbon content of 53.16 percent and a nitrogen content of 17.98 percent as compared with theoretical contents of 53.1 percent and 17.7 percent, respectively.

EXAMPLE 4 N- [3-(] ,2,4-lriazyl 3,5-dinitrobenzamide OzN 3-arnino-1,2,4-triazole (8.4 grams; 0.1 mole) was dissolved in 75 milliliters of pyridine at about 65 C. and 11.5 grams (0.05 mole) of 3,5-dinitrobenzoyl. chloride added portionwise thereto. The addition was carried out with stirring and at a temperature of 65 C. Upon completion of the reaction, the reaction mixture was cooled. During the cooling, a material precipitated in the mixture as a solid. The solid was separated by filtration, and successively washed with dilute aqueous sodium bicarbonate and water. As a result of these operations there was obtained an N-[3-(1,2,4-triazyl)] 3,5-dinitrobenzamide product asa crystalline solid having carbon, hydrogen and nitrogen contents of 39.58, 2.36 and 29.19 percent respectively, as compared to theoretical contents of 38.86, 2.17 and 30.3. N-[3-(l,2,4-triazyl)] 3,5-dinitrobenzamide has a molecular weight of 277.

EXAMPLE N-[4-(2,6-dimethylpyrimidyl)] 3,5-dinitrobenzamide 4-amino-2,6-dimethylpyrimidine (12.3 grams, 0.1 mole) was dispersed in 75 milliliters of pyridine and 23 grams (0.1 mole) of 3,5-dinitrobenzoyl chloride added portionwise thereto with stirring. During the addition, the temperature of the reaction mixture became quite warm to touch. Following the reaction, the reaction mixture was diluted with amixture of dilute aqueous hydrochloric acid and ice and thereafter filtered. The filtrate was then adjusted to a pH of from 5 to 6 by the addition of the sodium carbonate. During the addition of the carbonate, an N- [4-(2,6-dinitropyrimidyl)] 3,5-dinitrobenzamide hydrate product precipitated in the mixture as a crystalline solid. The product was separated :by filtration and recrystallized from ethanol. The recrystallized product had carbon, hydrogen and nitrogen contents of 46.57, 3.83 and 21.0 percent, respectively as compared to theoretical contents of 46.58, 3.91 and 20.91 percent. The product lost the solvent of crystallization upon heating and melted at 253.5 254.0 C. and had carbon, hydrogen and nitrogen contents of 49.15, 3.5 0 and 22.18 percent, respectively, as compared to theoretical contents of 49.20, 3.50 and 22.10 percent.

In a similar manner other compounds of the present invention are prepared as follows:

N-(3-pyrryl)3,5-dinitrobenzamide by reacting 3,5-dinitrobenzoyl chloride with 3-aminopyrrole.

N-(3-furyl) 3,5-dinitrobenzamide by reacting 3,5- dinitrobenzoyl bromide with 3-aminofuran.

N-(2-methyl-3-furyl) 3,5-dinitrobenzamide by reacting 3,5-dinitrobenzoyl chloride with 3-amino-2-methylfuran.

N-(2-oxazolyl) 3,5-dinitrobenzamide by reacting 3,5- dinitrobenzoyl chloride with 2-aminooxazole.

N-(S-isooxazolyl) 3,5-dinitrobenzamide by reacting 3,5-dinitrobenzoyl bromide with S-aminoisooxazole.

N-(3-methyl-4-isooxazolyl) 3,5-dinitrobenzamide by reacting 3,5-dinitrobenzoyl bromide with 4-amino-3- methylisooxazole.

N-(3-pyrry1) 3,5-dinitro-o-toluamide by reacting 3,5- dinitro-o-toluyl chloride with 3-aminopyrrole.

N-(Z-thienyl) 3,5-dinitro-o-toluamide by reacting 3,5- dinitro-o-toluyl chloride with 2-aminothiophene.

N-(2-pyrazolyl) 3,5-dinitro-o-to1uamide by reacting 3,5- dinitro-o-toluyl bromide with 2-aminopyrazole.

N-(3-pyrryl) 3,5-dinitro-Z-methoxybenzamide by reacting 3,5-dinitro-2-methoxybenzoyl chloride with 3- aminopyrrole.

N-(3-pyridazyl) 3,5-dinitro-2-methoxybenzamide by reacting 3,5-dinitro-2-methoxybenzoy1 chloride with 3- aminopyridazine.

N-(4-pyrimidyl) 3,5-dinitro-2-methoxybenzamide by reacting 3,S-dinitro-2-methoxybenzoyl chloride with 4- amino-pyrimidine.

N-(3-furyl) 3,5-dinitro-2-ethylbenzamide by reacting 3,S-dinitro-Z-ethylbenzoyl chloride with 3-aminofuran.

N-(2-pyridyl) 3,5-dinitro-2-ethylbenzamide by reacting 3,5-dinitro-2-ethylbenzoyl chloride with 2-amino-pyridine.

N-(Z-gammapicolyl) 3,5-dinitro-2-ethylbenzamide by reacting 3,5-dinitro-2-ethylbenzoyl chloride with 2-aminogar'nmapicoline.

N-2-(4,6-lutidyl) 3,5-dinitro-2-ethylbenzamide by reacting 3,5-dinitro-2-ethylbenzoyl chloride with 2-arnino- 4,6-lutidine.

The compounds of the present invention have been found to be useful as parasiticides and as anthelmintics for the control of gastro-intestinal parasites in warm blooded animals. In such use, the unmodified compounds are employed or compositions containing the compounds in admixture with an innocuous ingestible adjuvant or a finely divided solid such as alcohol, syrups, edible oils, chalk, bentonite grain rations, feed concentrates or supplements, or animal feeds. The products also are employed as constituents of aqueous dispersions or oil-inwater emulsions with or without the addition of surface active dispersing agents. In representative operations, the feeding as a sole ration to chickens of a commercial poultry mash containing 0.1 percent by weight of N-(Z-aminopyridyl) 3,5-dinitro-o-toluamide give substantially complete controls of Eimerz'a tenella and cecal coccidiosis in the birds.

The 3,5-dinitrobenzoyl halides or 3,5-dinitro-2-alkylbenzoyl halides employed as starting materials in accordance with the teachings of the present invention may be prepared by reacting a suitable 3,5-dinitroarenoic acid with thionyl chloride (SOCI thionylbromide or phosphorus pentachloride to produce the corresponding and desired acid halide. The 3,5-dinitro-Z-methoxybenzoyl halide employed as starting material may be prepared by reacting an alkali metal methoxide with an alkali metal salt of 3,5-dinitro-2-chlorobenzoic acid whereby a methoxy group is substituted for chlorine to produce an alkali metal salt of 3,5-dinitro-2-methoxybenzoic acid. The salt is then converted to the corresponding acid and thereafter reacted with thionyl halide to produce the desired starting material.

We claim:

N-[4-(2,6-dimethylpyrimidyl)] 3,5-dinitrobenzarnide.

References Cited UNITED STATES PATENTS 2,068,824 1/1937 Schonhofer et al. 260-2564 5 2,489,526 11/1949 Crowther et a1. 260256.4

OTHER REFERENCES Elion et al., J. Am. Chem. Soc., vol. 73, pages 5235-9 (1951).

ALTON D. ROLLINS, Primary Examiner.

WALTER MODANCE, N. S. RIZZO', ALEX MAZEL,

I. MARCUS, Examiners.

H. R. IILES, Assistant Examiner. 

